The long-range goal of this research is to characterize the CNS pathways that control basal sympathetic nerve discharge (SND) and cardiovascular function. Since 1990, the PI has studied the control of the 10-Hz rhythm that is the predominant feature of SND in decerebrate or urethane- anesthetized cats. This rhythm is highly coherent in nerves controlling a variety of cardiovascular target organs and may be a prerequisite for inducing the complex patterns of spinal sympathetic outflow that accompany some behavioral states. Studies during the current funding period are the first to identify specific CNS sites that regulate this activity. Data from antidromic activation experiments have indicated reciprocal connections between some of these areas and pharmacologic studies have suggested neurotransmitter systems that are important in the control of the 10 hz rhythm in SND. In the proposed 5-yr research plan, state-of-the-art electrophysiologic and analytic techniques will be combined with microiontophoresis and microinjection of drugs to address 4 Specific aims: (1) To test the hypothesis that pontine neurons in the A5, A6 and parabrachial/Kolliker- Fuse complex are involved in the control of the 10 Hz rhythm, (2) To identify the interconnections and signs (excitation or inhibition) of synaptic connections among brainstem neurons with activity correlated to the 10 Hz rhythm in SND, (3) To test the hypothesis that the 10 Hz rhythm is generated by a distributed network of brainstem neurons, and (4) to identify the central sites where serotonergic and catecholaminergic neurons act to affect the balance between the 10 Hz rhythm and the irregular 2-6 Hz oscillations in SND. These studies will enhance our understanding of the central circuitry responsible for generating and controlling the 10 Hz rhythm in resting SND.